Global longitudinal strain (GLS) declines throughout adult-life as the LV remodels and adapts. Information on the impact of cardiac risk factors such as male sex, obesity, smoking status, hypertension, hypercholesterolemia, and diabetes on GLS. over time has not yet been investigated. The present prospective longitudinal study included 689 participants of the 4th and 5th Copenhagen City Heart Study who had GLS measured at both timepoints. Mean age was 51 years and 45% were male. All participants underwent two echocardiographic examinations median 10.4 (IQR: 10.2, 10.9) years apart. Average decline in GLS during follow-up was -0.7%. High age, male sex, high body mass index, and mean arterial blood pressure (MAP) proved to be significantly associated with an accelerated decline in GLS. In a multivariable regression model including all the investigated cardiovascular risk factors, age (stand. beta-coef. = -0.10, P = 0.005), male sex (stand. beta-coef. = -0.16, P < 0.001), and MAP (stand. beta-coef. = -0.07, P = 0.009) were independent predictors of an accelerated decline in GLS during a 10-year period. Finally, the investigated risk factors had different regional impact after the same multivariable adjustments. Male sex had a significant impact on changes in longitudinal strain at the apical, mid-wall and basal segments, meanwhile MAP and age only accelerated changes in the mid-wall and basal longitudinal strain. In the general population age, male sex, and MAP are independent predictors of an accelerated decline in GLS over a 10-year period. Furthermore, MAP, male sex and age had different regional impact.